Isotopic measurement is notably performed in the nuclear area, and environment, geosciences and life sciences.
Isotopic measurement consists of determining the presence and/or concentration of one or more isotopes of a chemical element in a sample.
Each element of the periodic table has one or more isotopes, i.e. different atoms of one and the same element. Two isotopes of one and the same element have the same number of protons and electrons but a different number of neutrons.
Typically, iron, denoted Fe, has stable isotopes of masses 54, 56, 57 or 58 atomic mass units (amu) denoted 54Fe, 56Fe, 57Fe and 58Fe.
Determination of the isotopic ratios consists of measuring the abundance of each of these isotopes and calculating their respective proportions.
In the case of iron, the isotopic ratio 56Fe/57Fe equates to expressing the abundance of 56Fe relative to that of 57Fe.
Isotopic measurements notably make it possible to determine:
the isotopic abundances of the different isotopes of one and the same element,
the precise concentration of a particular element in solution by adding a known proportion of a tracer, the latter being perfectly characterized in terms of isotopic composition and concentration. This method is known as simple isotopic dilution,
the abundance ratio between two isotopes of different elements (e.g. 145Nd/238U) by adding a double isotopic tracer (e.g. 148Nd/233U) by the method called double isotopic dilution.
The method of simple isotopic dilution consists of adding a tracer that is the same element but of different isotopic composition, for example enriched in one of the isotopes of the element to be determined, to the sample. This method makes it possible to effect elemental measurements of great precision, without a calibration straight line, as the isotopic composition and the concentration of the tracer are known perfectly, and based on measurement of the isotopic ratios.
Isotopic measurements require the use of instruments, such as mass spectrometers, capable of supplying a selective response to one or more given atomic masses, the intensity of the response having to be proportional to the abundance of the isotopes.
The technique most commonly used is ICP-MS. Spectrometers of the ICP-MS type consist of a plasma torch and a mass spectrometer. The plasma torch generally contains a rare gas (argon in most cases) which, under the action of an electric discharge and a radiofrequency field, generates a plasma that ionizes, with an efficiency close to 1, most of the elements introduced into the torch in elemental form or as compounds. Spectrometry of the ICP-MS type has been an indispensable analytical technique for many years. It allows rapid analysis of the majority of the elements of the periodic table qualitatively and quantitatively, while having good reproducibility, sensitivity, resolution, and a linear relation between the amount of the species to be analysed and the signal detected.
To obtain the best possible precision for measuring isotopic ratios, it is necessary to use a multicollector ICP-MS (MC-ICPMS), which allows the abundance of several isotopes to be measured simultaneously. This type of equipment notably is free from the instability of the ion beam at the level of the source of the mass spectrometer.
However, when the solution to be analysed comprises several charged species of very similar atomic mass (isobaric), prior to measurement it is necessary to separate the species individually with a chemical separative technique such as liquid chromatography or capillary electrophoresis.
In fact, despite the high resolving power of spectrometers of the ICP-MS type, they are not capable of resolving or differentiating all the isobaric interferences.
Isobaric interference is the term used when two isotopes of different elements have atomic masses whose difference is between 0.001 and 0.9 atomic mass unit.
For example, separation of two isotopes of two different elements such as neodymium of exact mass 149.9209 (150Nd) atomic mass units (amu) and samarium (150Sm) of exact mass 149.9173 amu requires a resolving power above 40000, well above the capabilities of spectrometers of the ICP-MS type.
Resolving power means the ability of a mass spectrometer to separate an ion of mass M from an ion of mass M+ΔM, with R=M/(M+ΔM).
In practice, a chemical separative technique and a spectrometer of the ICP-MS type may be combined by indirect coupling or “off-line”, or by direct coupling or “on-line”.
In indirect coupling, isotopic measurement is performed twice.
Firstly, the species contained in the solution are separated and then collected individually at the end of the separative technique. Secondly, each fraction collected is dried by heating, put back in solution with dilute nitric acid and then analysed with the spectrometer of the ICP-MS type. Each fraction then contains a single species (a single element) and there is no longer isobaric interference. The signal measured by the spectrometer of the ICP-MS type is stationary or constant as the solution containing the element previously separated is introduced continuously, which has the advantage of ensuring stability during the measurements of isotopic ratios, and consequently improving the measurement precision.
However, indirect coupling has the drawback of requiring steps of collection and treatment of previously separated fractions. These steps are difficult to automate and significantly increase the duration of the whole analysis process.
In direct coupling, isotopic measurement is performed in a single sequence. Once separated, the species are introduced directly, or in other words, introduced into the spectrometer of the ICP-MS type without a time gap between each species. Coupling of the chemical separation technique with the spectrometer is effected via a suitable interface. Direct coupling therefore dispenses with treatment of the collected fractions that is inherent in indirect coupling, notably making it possible to reduce the analysis time.
Thus, the document “Pitois A. et al., International Journal of Mass Spectrometry, 2008, 270, pages 118-126” proposes isotopic measurement in which fission products of a solution of nuclear fuel are separated by electrophoresis using a capillary electrophoresis device connected by direct coupling to a spectrometer of the ICP-MS type.
FIG. 1 shows a flow sheet of isotopic measurement by direct coupling via a coupling interface 10 between a device for separating the species and a mass spectrometer of the ICP-MS type, the coupling interface 10 comprising a nebulizer 9 in the figure and a sorting chamber 12. On leaving the separating device 20, the species to be analysed A, B, C are introduced into the nebulizer 9, in which the species A, B, C are transformed into aerosol comprising fine droplets and a carrier gas (generally argon). The number of species to be analysed can of course be greater than three.
The finest droplets comprising the species A, B, C are then selected in a sorting chamber 12 so as to convey a stable, homogeneous aerosol to the plasma torch 13 of the ICP-MS spectrometer. On leaving the plasma torch 13, the species A, B, C are desolvated, atomized and ionized. The ions are then extracted from the plasma by means of extraction cones 14 and then focused by focusing lenses 15, before entering the ICP-MS spectrometer. Under the action of a magnetic field generated by a magnet 16, the ion beams corresponding to the different isotopes are separated following individual circular paths that depend on the mass/charge ratio of the isotopes to be analysed. Information on the abundance of the isotopes is obtained by placing in their path detectors 17, which record, simultaneously and continuously, the intensity of each of the beams of mono-isotopic ions. MC-ICPMS spectrometers generally have from 9 to 16 detectors 17.
Another document of the prior art EP 2646813 discloses a method for isotopic measurement in which coupling between the separative technique and the ICPMS spectrometer notably allows measurement that can be automated and is of reduced duration, with improved reproducibility and resolution, in particular when the solution comprises several elements having one or more isobaric interferences.
The separative methods used conventionally, such as chromatography or electrophoresis, allow individual separation of the species A, B, C, which are eluted in the form of single-element peaks of triangular shape, as shown schematically in FIG. 2a. 
This type of peak only allows a small number of measurement points in unit time.
Moreover, there are large variations of signal amplitude between two consecutive points, which cause instability and especially imprecision of measurement by the spectrometer of the ICP-MS type.
In the isotachophoresis configuration of an electrophoresis device, once separation has been performed, elution takes place in the form of bands, as shown in FIG. 2b, thus allowing more precise measurements to be obtained.
Isotachophoresis (ITP) is a method for separating species as a function of their electric charge/size ratio. The device used for carrying out this method is a conventional capillary electrophoresis device.
The capillary electrophoresis device consists essentially of two reservoirs connected by a capillary column, each reservoir containing an electrolyte and an electrode. After a voltage is applied between the two electrodes, the species introduced into the capillary filled with electrolyte separate according to their speed of electrophoretic migration, which is a function of their electric charge/size ratio. The separated species are then detected using a suitable analytical technique.
The isotachophoresis mode of capillary electrophoresis is characterized by the use of a discontinuous separation medium comprising a leading electrolyte M and a terminating electrolyte T of different composition, between which the solution S to be analysed is inserted contiguously. The leading electrolyte M has the highest speed of electrophoretic migration of the device, and the terminating electrolyte T has the lowest speed of electrophoretic migration of the device. The leading electrolyte M and terminating electrolyte T are positioned after the inlet and before the outlet of the capillary, respectively.
The composition of the electrolytes must therefore take account of the value of the speeds of electrophoretic migration of the species, otherwise these species will not be separated.
After a voltage is applied between the ends of the capillary (capillary inlet and outlet), the species, under the effect of a current of constant intensity or of a constant electric field, will gradually become arranged according to their speed of electrophoretic migration until a state of equilibrium is reached called quasi-stationary. The species are then distributed in their individual, clearly delimited contiguous elution bands. The species are therefore concentrated or diluted as a function of their initial concentration in the solution.
Isotachophoresis therefore differs from the conventional implementation of capillary electrophoresis by the use of a discontinuous separation medium, comprising at least two electrolytes instead of just one, but also by the fact that, since the concentration of a species is homogeneous at all points of the elution zone obtained in isotachophoresis, its detection is reflected in a signal of constant or approximately constant amplitude within this zone, rather than a peak reflecting a variation of concentration over time. The number of measurement points that can be recorded by the ICP-MS spectrometer depends on the width of the elution zone.
The principle of separation by isotachophoresis may be summarized as shown in FIGS. 3a-3c. 
A leading electrolyte M, a solution S comprising the species A, B and C, and a terminating electrolyte T are injected in that order into a capillary 30, with the terminals of the capillary 30 connected to a voltage generator designated I (FIG. 3a).
The leading electrolyte M determines the speed of electrophoretic migration, and it is selected so as to have the highest speed of electrophoretic migration of the system.
In contrast, the terminating electrolyte T has the lowest speed of electrophoretic migration of the system.
The composition of the electrolytes must therefore take account of the species of interest, otherwise these species will not be separated. The leading M and/or terminating T electrolytes generally have a concentration between 1 mM and 100 mM, preferably between 10 mM and 20 mM. They generally possess buffering power.
The terminating electrolyte T may be a zwitterionic compound such as carnitine chloride or a carboxylic acid such as acetic acid. Preferably, the leading electrolyte M and terminating electrolyte T are aqueous solutions comprising elements such as oxygen, hydrogen, nitrogen and carbon so as to allow easy destruction at the end of analysis.
Under the effect of the current of constant intensity (or constant electric field) from some tens of nanoamperes to some tens of microamperes (or from some volts to kilovolts, respectively), the species A, B and C are reorganized as a function of their speed of electrophoretic migration, creating a gradient of speed between the terminating electrolyte T and the leading electrolyte M (FIG. 3b).
At the end of this reorganization (FIG. 3c), the species A, B and C are separated and concentrated in contiguous single-element bands between the leading electrolyte M and the terminating electrolyte T. The species A, B and C as well as the leading M and terminating T electrolytes then migrate at an identical speed imposed by the leading electrolyte M.
The performance of an isotachophoresis separation system is defined by the concept of resolution or degree of purification of the species.
Ohm's law (Equation 1), which applies during separation, relates the conductivity a of a sample to the length L and to the inside diameter d of the capillary 30 as well as to the value of voltage U of the voltage generator.
                    U        =                                            4              ⁢              I                        πσ                    ·                      L                          d              2                                                          (                  Equation          ⁢                                          ⁢          1                )            
When a solution S comprising a high concentration of one of the elements relative to the trace elements is injected, it is necessary to increase the amount of solution S to be injected into the capillary 30 so as to obtain bands comprising the trace elements of significant length, which improves the separation capacity.
This optimization of the separation capacity involves reducing the inside diameter d of the capillary 30 or increasing the length of the capillary L.
For example, if the size of the capillary is 3 m and the voltage is 30 kV, a voltage of 1 kV is obtained for each 10 cm fraction. If the length of the capillary is increased to 30 m, the voltage at the terminals of a fraction of length 10 cm drops to 0.1 kV.
To maintain a voltage of 30 kV at the terminals of the capillary 30, it would be necessary to keep the length L of the capillary 30 and increase the inside diameter d, which would degrade the separation capacity of the system.
A work by F. M. Everaert et al. “Isotachophoresis, experiments with electrolyte counterflow”, J. Chromatogr. 60(1971) 397-405, proposes applying a continuous counter-pressure in the direction opposite to the direction of electrophoretic migration of the species A, B and C so as to slow down the speed of migration of the species.
Another work by S. Bhattacharyya et al. “Sample dispersion in isotachophoresis with Poiseuille counterflow”, Phys. Fluids 25 (2013) also investigates this possibility. This study concludes that the application of a continuous counter-pressure during separation of the species by isotachophoresis is accompanied by an increase in dispersion, which reduces the efficiency of purification of the species, and particularly of the trace elements.